4CBN

Crystal structure of Complement Factor D mutant R202A after conventional refinement


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Ensemble Refinement Shows Conformational Flexibility in Crystal Structures of Human Complement Factor D

Forneris, F.Burnley, B.T.Gros, P.

(2014) Acta Crystallogr D Biol Crystallogr 70: 733

  • DOI: https://doi.org/10.1107/S1399004713032549
  • Primary Citation of Related Structures:  
    4CBN, 4CBO

  • PubMed Abstract: 

    Human factor D (FD) is a self-inhibited thrombin-like serine proteinase that is critical for amplification of the complement immune response. FD is activated by its substrate through interactions outside the active site. The substrate-binding, or `exosite', region displays a well defined and rigid conformation in FD. In contrast, remarkable flexibility is observed in thrombin and related proteinases, in which Na(+) and ligand binding is implied in allosteric regulation of enzymatic activity through protein dynamics. Here, ensemble refinement (ER) of FD and thrombin crystal structures is used to evaluate structure and dynamics simultaneously. A comparison with previously published NMR data for thrombin supports the ER analysis. The R202A FD variant has enhanced activity towards artificial peptides and simultaneously displays active and inactive conformations of the active site. ER revealed pronounced disorder in the exosite loops for this FD variant, reminiscent of thrombin in the absence of the stabilizing Na(+) ion. These data indicate that FD exhibits conformational dynamics like thrombin, but unlike in thrombin a mechanism has evolved in FD that locks the unbound native state into an ordered inactive conformation via the self-inhibitory loop. Thus, ensemble refinement of X-ray crystal structures may represent an approach alternative to spectroscopy to explore protein dynamics in atomic detail.


  • Organizational Affiliation

    Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
COMPLEMENT FACTOR D
A, B
228Homo sapiensMutation(s): 1 
EC: 3.4.21.46
UniProt & NIH Common Fund Data Resources
Find proteins for P00746 (Homo sapiens)
Explore P00746 
Go to UniProtKB:  P00746
PHAROS:  P00746
GTEx:  ENSG00000197766 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00746
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.219 
  • R-Value Work: 0.190 
  • R-Value Observed: 0.191 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.14α = 90
b = 67.31β = 90
c = 133.14γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
iMOSFLMdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-12-18
    Type: Initial release
  • Version 1.1: 2014-03-12
    Changes: Database references
  • Version 1.2: 2014-03-19
    Changes: Database references
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description